Authors: Solas C.; Poizot-Martin I.¹; Drogoul M-P.¹; Ravaux I.²; Dhiver C.²; Lafeuillade A.³; Allegre T.⁴; Mokhtari M.⁵; Moreau J.⁵; Lepeu G.⁶; Petit N.⁷; Durand A.⁸; Lacarelle B.⁸

Source: British Journal of Clinical Pharmacology, Volume 57, Number 4, April 2004 , pp. 436-440(5)

Publisher: Wiley-Blackwell

Abstract:

Aims

To evaluate the interindividual variability in the plasma concentrations of lopinavir in the context of routine monitoring with or without treatment with a non-nucleoside reverse transcriptase inhibitor and to assess the interaction between the coformulation of lopinavir/ritonavir and efavirenz or nevirapine. Methods

Plasma trough and peak concentrations (C_trough, C_max) of lopinavir from 182 HIV-1-infected patients were analysed by high-performace liquid chromatography. Three lopinavir/ritonavir regimens were assessed, namely (A) 400 mg lopinavir/100 mg ritonavir twice daily given alone (n = 125), (B) 400/100 mg twice daily together with a non-nucleoside reverse transcriptase inhibitor (n = 25), and (C) 533/133 mg twice daily together with a non-nucleoside reverse transcriptase inhibitor (n = 32). Results

Median (ng ml^-1) C_trough and C_max lopinavir (interquartile range, CV) were: (A) 4852 (3198–6891, 56%) and 8501 (6333–11 584, 41%), (B) 2979 (1704–5186, 74%) and 5612 (3362–11 704, 76%) and (C) 5082 (2696–7226, 74%) and 9757 (4883–12 963, 60%). Median C_trough of lopinavir was lower in patients taking both efavirenz [P = 0.01, 95% confidence interval (CI) for difference between medians 343, 2713] and nevirapine (P = 0.019, 95% CI for difference between medians 354, 3681) compared with those taking lopinavir/ritonavir alone. A higher interindividual variability was observed when lopinavir/ritonavir was given with a non-nucleoside reverse transcriptase inhibitor. The risk of achieving a ‘suboptimal’C_trough of lopinavir (below a threshold of 3000 ng ml^-1) was statistically higher in patients treated with a non-nucleoside reverse transcriptase inhibitor (P < 0.001, 95% CI for difference between percentages 8.8, 43.1%) compared with those receiving lopinavir/ritonavir alone. Conclusions

Our results confirmed the interaction between lopinavir and efavirenz, and also demonstrated a significant interaction between the former drug and nevirapine, resulting in lower C_trough of lopinavir. The wide interpatient variability in this interaction suggests that therapeutic drug monitoring may be useful in optimizing the dose of lopinavir.

Keywords: drug interaction; pharmacokinetic; protease inhibitors

Document Type: Research article

DOI: http://dx.doi.org/10.1046/j.1365-2125.2003.02020.x

Affiliations: 1: Department of Haematology, AP-HM Sainte-Marguerite, Marseille, France, 2: Department of Infectious Diseases, AP-HM Conception, Marseille, France, 3: Department of Infectious Disease, Chalucet Hospital, Toulon, France, 4: Department of Internal Medicine–Haematology, General Hospital of Aix, Aix en Provence, France, 5: Department of Infectious Disease, AP-HM Nord, Marseille, France, 6: Department of Internal Medicine and Infectious Diseases, Henri Duffaut Hospital, Avignon, France, and 7: Department of Internal Medicine, AP-HM Sainte-Marguerite, Marseille, France 8: Department of Pharmacokinetics, AP-HM Timone, Marseille, France,

Publication date: 2004-04-01

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